title: Discovery of non-peptide, small molecule antagonists of α9α10 nicotinic acetylcholine receptors as novel analgesics for the treatment of neuropathic and tonic inflammatory pain.
abstract: A series of azaaromatic quaternary ammonium analogs has been discovered as potent and selective α9α10 nicotinic acetylcholine receptor (nAChR) antagonists. The preliminary structure-activity relationships of these analogs suggest that increased rigidity in the linker units results in higher potency in inhibition of α9α10 nAChRs and greater selectivity over α7 nAChRs. These analogs represent a new class of analgesic for the treatment of neuropathic and tonic inflammatory pain.
authors.affiliation: College of Pharmacy, Department of Pharmaceutical Sciences, University of Kentucky, Lexington, KY 40536 0082, USA.
authors.forename: Guangrong
authors.initials: G
authors.lastname: Zheng
authors.forename: Zhenfa
authors.initials: Z
authors.lastname: Zhang
authors.forename: Cheryl
authors.initials: C
authors.lastname: Dowell
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Wala
authors.forename: Linda P
authors.initials: LP
authors.lastname: Dwoskin
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Holtman
authors.forename: J Michael
authors.initials: JM
authors.lastname: McIntosh
authors.forename: Peter A
authors.initials: PA
authors.lastname: Crooks
mesh_terms: D000700:Analgesics / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D000818:Animals; D004353:Drug Evaluation, Preclinical; D018733:Nicotinic Antagonists / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D010146:Pain / Q000188:drug therapy*; D000644:Quaternary Ammonium Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use; D051381:Rats; D011978:Receptors, Nicotinic / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000700:Analgesics; C470699:Chrna10 protein, rat; C498541:Chrna9 protein, rat; D018733:Nicotinic Antagonists; D000644:Quaternary Ammonium Compounds; D011978:Receptors, Nicotinic